Contemporary analysis of the influence of acute kidney injury after reduced intensity conditioning haematopoietic cell transplantation on long-term survival

Abstract

We evaluated retrospectively the incidence of acute kidney injury (AKI), defined by risk, injury, failure, loss and end-stage kidney disease (RIFLE) and its influence on long-term survival, in 82 patients aged 18-60 years who underwent a reduced intensity conditioning (RIC) haematopoietic cell transplantation (HCT). Patients (53.6%) developed AKI after HCT: 25% were on risk, 45.5% on injury and 29.5% on failure. In all, 64 patients survived after 100 days of post transplant and were available for long-term survival analysis. At follow-up, 43.7% of patients died. A 5-year overall survival of AKI patients was 41.6% as compared with 67.1% for those who did not develop AKI (P ¼ 0.028), and decreased according to AKI severity (risk, 55.6%; injury plus failure, 33.3%; P ¼ 0.045). After adjusting for age, history of cardiovascular disease, high-risk disease and chronic GVHD, AKI predicted 5-year overall mortality (AKI: adjusted hazards ratio (AHR), 2.36, 95% CI: 1.03-5.37; P ¼ 0.041). Moreover, moderate and severe AKI (injury plus failure) was also associated with an increased 5-year overall mortality (injury plus failure: AHR, 1.64, 95% CI: 1.06-2.54; P ¼ 0.024). According to RIFLE, 53.6% of patients had AKI after RIC HCT. Such patients have poor longterm survival, particularly in moderate or severe AKI.

An autopsy case that manifested no convincing histological changes of severe renal failure after hematopoietic stem cell transplantation

“…At present, there are three major HSCT modalities: autologous HSCT, myeloablative allogeneic HSCT, and non-myeloablative allogeneic HSCT, with selection depending on disease status and comorbidity. AKI is a common complication of all these HSCT modalities, although the incidence, severity, and impact on mortality differ among them [7][8][9][10].…”

Acute kidney injury in HCT: an update

“…28 As previously mentioned, AKI is also common in nonmyeloablative HCT, affecting up to half of the transplanted Acute kidney injury in HCTpatients, with the majority of these cases occurring in the second month after transplantation. 11,12 The longer time to AKI occurrence in non-myeloablative HCT as compared with myeloablative regimens can be explained by the lower prevalence of infectious complications and organ failure, especially hepatic SOS. It should be noted that patient outcome can differ according to the timing of AKI onset in the HCT setting.…”

“…23,24 Furthermore, severe GVHD with diarrhea and consequent dehydration, as well as CMV reactivation due to treatment of GVHD with high-dose prednisolone can likewise contribute to GVHD-associated nephrotoxicity. 12,25 Second, since there are no foreign cells in myeloablative autologous HCT, engraftment occurs more rapidly (resulting in less cytopenia, sepsis and antimicrobe-induced nephrotoxicity).…”

“…8 Although these classifications allowed for the identification of a significant number of patients as having AKI after myeloablative and non-myeloablative HCT, and performed well in predicting patient outcome, the advantages of each one over the other remain to be established in this setting. [9][10][11][12][13] The KDIGO classification system 14 (Table 1) proposed in 2012 resulted from the fusion of the former classifications (RIFLE and AKIN) as a means to establish one classification of AKI for clinical practice, research and public health. In the HCT setting, the KDIGO classification has not yet been prospectively evaluated, and it has only been employed in a recently published retrospective study of a small cohort of critically-ill allo-HCT patients.…”

“…The major culprit for AKI in nonmyeloablative HCT is calcineurin inhibitors injury by themselves or in association with other etiologies, namely sepsis, nephrotoxicity or GVHD. 12,32,33 In both myeloablative allogeneic and nonmyeloablative HCT, calcineurin inhibitors are employed as prophylaxis against GVHD. One of the most common and serious complications associated with calcineurin inhibitors is their nephrotoxicity, manifested as AKI (mostly reversible after dose reduction) or as progressive CKD (usually irreversible).…”